Proteomic Identification of Putative Biomarkers of Radiotherapy Resistance
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December 6, 2012
Lynn Cawkwell, Senior Lecturer, University of Hull
Abstract
The proteomic analysis of radioresistant cancer cell lines may identify proteins which could be used as predictive biomarkers in order to individualise treatment for cancer patients. We established 7 novel radioresistant cancer cell sublines from parental breast cancer cells, oral cancer cells and rectal cancer cells. Three complementary comparative proteomics methods were used to identify differentially expressed proteins (DEPs) in RR cells when compared with the respective parental cells. An antibody microarray platform containing 725 antibodies was utilised in addition to 2 dimensional gel electrophoresis with MALDI TOF/TOF mass spectrometry (MS) and quantitative iTRAQ analysis. The DEPs identified were mapped onto canonical signalling pathways using Ingenuity Pathway Analysis (IPA) and a selection of proteins investigated further using immunoblotting and immunohistochemistry. Clinical validation of selected proteins within key canonical pathways, including the p53, ATM and ubiquitin-proteasome signalling pathways, is ongoing in order to identify a panel of predictive biomarkers of radioresistance.
